TY  - JOUR
A1  - Hinderer, Svenja
A1  - Shen, Nian
A1  - Ringuette, Léa-Jeanne
A1  - Hansmann, Jan
A1  - Reinhardt, Dieter P
A1  - Brucker, Sara Y
A1  - Davis, Elaine C
A1  - Schenke-Layland, Katja
T1  - In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold
JF  - Biomedical Materials
N2  - Elastic fibers are essential for the proper function of organs including cardiovascular tissues such as heart valves and blood vessels. Although (tropo)elastin production in a tissue-engineered construct has previously been described, the assembly to functional elastic fibers in vitro using human cells has been highly challenging. In the present study, we seeded primary isolated human vascular smooth muscle cells (VSMCs) onto 3D electrospun scaffolds and exposed them to defined laminar shear stress using a customized bioreactor system. Increased elastin expression followed by elastin deposition onto the electrospun scaffolds, as well as on newly formed fibers, was observed after six days. Most interestingly, we identified the successful deposition of elastogenesis-associated proteins, including fibrillin-1 and -2, fibulin-4 and -5, fibronectin, elastin microfibril interface located protein 1 (EMILIN-1) and lysyl oxidase (LOX) within our engineered constructs. Ultrastructural analyses revealed a developing extracellular matrix (ECM) similar to native human fetal tissue, which is composed of collagens, microfibrils and elastin. To conclude, the combination of a novel dynamic flow bioreactor and an electrospun hybrid polymer scaffold allowed the production and assembly of an elastic fiber-containing ECM.
KW  - elastin
KW  - elastic fibers
KW  - electrospinning
KW  - tissue engineering
KW  - regenerative medicine
KW  - heart valve
KW  - cardiovascular
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254074
VL  - 10
IS  - 3
ER  -